Increasing incidence and costs of the treatment of malign tumors are a significant medical problem with direct and undesirable impact on the whole society. A typical example are the malignant neoplasia of the breast that represent the second most frequent malignancy in women living in developed countries. During the last 25 years the number of newly reported breast cancers in the Czech Republic increased almost twice. It ensues from the Czech National Oncology Registry (NOR) latest complete data that in 2004 the absolute number of new cases achieved 5628 patients, i.e., the incidence of 107.4 per 100 000 of women and the mortality of 40.06 per 100 000 of women (www.svod.cz). In approximately 20 to 25% of the patients the breast carcinoma shows an excessive expression of HER-2 receptor (hereinafter reported as HER-2 positive carcinomas) that usually originates on the basis of amplification of the gene. Those carcinomas are characterized by high degree of aggressiveness and, therefore, adverse prognosis. On the other hand, there exists an efficient therapy, targeted against the HER-2 receptor. It is for instance the monoclonal antibody trastuzumab that is indicated at present for adjuvant and palliative treatment of HER-2 positive breast carcinoma patients. In combination with chemotherapy this antibody brings, in case of adjuvant treatment, a significant decrease of the disease recurrence and, consequently, an increase of the number of cured patients, or a significant extension of life if administered to the patients with disseminated disease.
Despite the fact that trastuzumab is administered to a narrowly selected group of HER-2 positive carcinoma patients, the clinical response is variable, namely, both as to the tumor response and to period of duration. In general, it occurs in approximately 40% of the cases. The causes of resistance of the disease to trastuzumab are not determined unambiguously. It may be a damaging of HER-2 receptor that is not then capable of its own kinase activity or binding of the monoclonal antibody of trastuzumab. Alterated may also be the individual signaling pathways of the HER-2 receptor or their regulators. Analogically to the targeted treatment directed at the HER-2 receptor, the problems of the need of rational indication of targeted treatment are solved in a similar manner also in the therapy directed at the other members of the HER gene family, e.g., HER-1 receptor and its inhibition by cetuximab, gefitineb or erlotinib. Those medicaments are indicated for other tumor diseases, e.g., cetuximab for HER-1 positive carcinoma of the colorectum, head and neck, or gefitinib or erlotinib for carcinoma of the lungs, pancreas and in other indications. The increasing number of clinical studies under progress documents high efficiency of the inhibitors directed to HER family in a number of clinical indications where the classical cytotoxic treatment is insufficiently efficient, nevertheless, not all patients benefit even from this targeted treatment and again, in case of the majority of roughly more than a half of the patients this treatment fails. With regard to high homology of the individual members of the HER family and similarity of their signaling pathways it is possible to assume that the efficiency biomarkers are similar.